delirium paul borghesani md-phd assistant professor psychiatry and behavioral sciences [email protected]
TRANSCRIPT
Delirium:Defining delirium
“an acute mental disturbance characterized by confused thinking and disrupted attention usually accompanied by disordered speech
and hallucinations”
akaacute confusional state
acute brain failureencephalopathy
global cognitive impairmentHippocrates “phrenitis”
“the great imitator”
Delirium:A gestalt
EtiologyCognitivedysfunctio
nPathophysiology
?Neuronal levelSystems level
Goals for today
Review the epidemiology and importance of detecting delirium
Learn the key features and subtypes of delirium
Explore the pathophysiology of delirium
Learn how to evaluate and treat delirium
Learn to recognize co-morbid delirium in mental illness
Who could be delirious?
An agitated, combative patient who does not follow instructions
An obtunded, minimally interactive patient
An emotionally erratic patient who makes contradictory remarks and who staff cannot logically engage
A calm, confused patient who is suspicious and oppositional
Clinical case:31 y/o with confusion
A 31 y/o previously healthy male is brought in by his roommate secondary to acute change in mental status. The patient is confused and bewildered and appears anxious and agitated. He denies medical problems and states that he takes medications for anxiety but cannot explain any details. He reports nausea, headache, tremor and myoclonus. He has mildly elevated WBC but his labs and vitals are within normal limits.
Questions:1)What factors suggest this is delirium?2)What is a possible etiology?
Clinical case:31 y/o with confusion
A 31 y/o previously healthy male is brought in by his roommate secondary to acute change in mental status. The patient is confused and bewildered and appears anxious and agitated. He denies medical problems and states that he takes medications for anxiety but cannot explain any details. He reports nausea, headache, tremor and myoclonus. He has mildly elevated WBC but his labs and vitals are within normal limits.
Questions:1)What factors suggest this is delirium?2)What is a possible etiology?
Clinical keys of delirium
Abrupt onset
Fluctuating symptoms
Difficulty sustaining attention
Appear to have cognitive dysfunction
Clinical case:31 y/o with confusion
A 31 y/o previously healthy male is brought in by his roommate secondary to acute change in mental status. The patient is confused and bewildered and appears anxious and agitated. He denies medical problems and states that he takes medications for anxiety but cannot explain any details. He reports nausea, headache, tremor and myoclonus. He has mildly elevated WBC but his labs and vitals are within normal limits.
Questions:1)What factors suggest this is delirium?2)What is a possible etiology?
Perry and Wilborn. Annals of Clinical Psychiatry. 24(2) 155 (2012)
Clinical case:Serotonin syndrome (SS)
Can be caused by any antidepressant
Most cases are associated with polypharmacy
Typical symptoms include- mental status changes, tremor, myoclonus, hyperreflexia, GI
symptoms, diaphoresis, fever, inducible clonus
Most often confused with neuroleptic malignant syndrome
- SS is associated with GI symptoms, myoclonus, mild or no laboratory changes
- NMS is associated with more severe rigidity and laboratory changes (low Fe, dramatically elevated creatine kinase, elevated WBCs)
Epidemiology and diagnosis of delirium
Hall R et at. Best Pract & Research Clin Anaesth, 2012 Inouye, S.K. N Engl J Med, 2006.
Epidemiology of delirium:It’s common!
Common in the general population- 0.4% of all people
- 1.0% in individuals over 55 (over 10% in those > 85)
- 60% of nursing home residents
Common in the medical setting- 10-30% of elderly in the ER
- 20% of all medical admissions
- 4-53% among hip fracture patients
- 4-28% of elective surgery patients
- 13-72% of cardiac surgery patients
Consequences of delirium
Increased length of stay
Increased mortality and morbidity- Perhaps between 25-75%, as high as MI and sepsis
Prolonged cognitive difficulties
Institutionalization
DSM-5
Delirium:DSM-5 diagnostic criteria
A. A disturbance in attention and awareness
B. The disturbance develops over a short period of time, represents a change in function, and fluctuates
C. There is a disturbance in cognitionmemory, disorientation, language, visuospatial ability, or perception
D. A and C are not better explained by an established neurocognitive disorder
E. Evidence from the history, PE or laboratory findings that this represents another medical condition, substance intoxication or withdrawal, toxin exposure or due to multiple etiologies.
DSM-5
Delirium:DSM-5 specifiers
Specify etiology- Substance intoxication delirium
- Substance withdrawal delirium
- Medication-induced delirium
- Delirium due to another medical condition
- Delirium due to multiple etiologies
Specify characteristics- acute (hours to days) or persistent (weeks to months)
- hyperactive, hypoactive or mixed
Classification of delirium: Hyperactive subtype
Agitated, uncooperative and often combative
Psychotic and responding to internal stimuli
Loud and fast speech
Wandering, restless
Appear intoxicated
Classification of delirium:Hypoactive subtype
Somnolent, inattentive, and uninterested
Poor memory and cognitive abilities
Will be described as having lapses or variable behavior
Reduced amount and rate of speech
Often missed because they can be left alone
Classification of delirium:Mixed subtype
Combination of both
Hypoactive and mixed account for about 80% of all cases
DSM-5
Delirium:Other DSM-5 delirium syndromes
Other specified delirium- the full criteria for delirium are not met
- you choose to specify WHY the criteria are not met
- e.g., “attenuated delirium syndrome”
Unspecified delirium- the full criteria for delirium are not met
- you choose NOT to specify why the criteria are not med
- often appropriate in the ED when etiologies are unknown
Clinical case:44 y/o non-compliant patient
A 44 y/o male is sustained multiple injures after being hit by a car. Two days after surgical admission psychiatry is consulted secondary to his variable refusal of care and an attempted elopement. He is described as intermittently yelling, throwing food, and RISing. He is homeless, has known mental illness and a history of alcoholism. The surgical team is asking if he has capacity to refuse care. When you meet with him he is disoriented to time and circumstance and is often incomprehensible because of mumbling and tangentiality.
Questions:1)What suggests he is having visual hallucinations?2)What is a possible etiology of his delirium?
Clinical case:44 y/o non-compliant patient
A 44 y/o male is sustained multiple injures after being hit by a car. Three days after surgical admission psychiatry is consulted secondary to his variable refusal of care and an attempted elopement. He is described as intermittently yelling, throwing food, and RISing. He is homeless, has known mental illness and a history of alcoholism. The surgical team is asking if he has capacity to refuse care. When you meet with him he is disoriented to time and circumstance and is often incomprehensible because of mumbling and tangentiality.
Questions:1)What suggests he is having visual hallucinations?2)What is a possible etiology of his delirium? (Hint: he vitals are
unstable)
Clinical case:Delirium tremens
Onset 2-3 days after last drink
Peaks 4-5 days
Severe autonomic hyperactivity- fever, tachycardia, tachypnea, hypertension, tremor diaphoresis
Delirium- confusion, disorientation, agitation, perceptual disturbances including
visual hallucinations
- may/may not be accompanied by seizures
Treat with benzodiazepines
Must have Features 1 & 2 and either 3 or 4
The confusion assessment method (CAM):An alternative to the DSM-5
Feature 1: Acute onset or fluctuating course- usually obtained from an informant
Feature 2: Inattention- from your evaluation, are they distractible or unable to follow the
conversation
Feature 3: Disorganized thinking- rambling, confused, derailment, illogical, loose associations
Feature 4: Altered level of consciousness - normal to comatose
Levels of consciousness
Agitated (out of control)
Hyperalert (vigilant)
Alert (normal)
Drowsy (lethargic)
Obtunded (difficult to wake)
Stuporous (v. difficult to wake)
Comatose (unable to wake)
http://www.icudelirium.org/docs/CAM_ICU_training.pdf
van den Boogaard et al. BMJ 2012
Using the PRE-DELIRIC:PREdiction of DELIRium in ICu patients
Diagnosis of delirium:Differentiating it from mental illness
Age of onset and history of mental illness
Assess risk factors for delirium
Disorientation
Reduced level of alertness and fluctuations
Speech not typically dysarthric in mental illness (except in intoxication or withdrawal)
Visual hallucinations are atypical
Algahtani and Abdu. Neurosciences 17(3) 205 (2012)
Diagnosis of delirium:Differentiating it from dementia
Delirum Dementia
Attention impaired intact early, impaired late
Course acute, fluctuating chronic, progressive
Speech rambling, mumbling impoverished
Perception illusions and hallucinations often normal
Thinking disorganized impoverished
Alertness agitated/obtunded normal
Clinical case:79 y/o with confusion
A 79 y/o male who is being treated for a pneumonia is referred to psychiatry consults for after waking up at night screaming and disoriented. The consult resident establishes that the patient’s attention is poor, their memory is impaired, and their speech and behavior is disorganized. They believe he is delirious and are considering treatment with haloperidol.
Questions:1)What is the KEY historical point missing?2)What should be done before recommending haloperidol?
Etiology, pathophysiology and clinical assessment of delirium
Etiology:General principles
Trying to establish and etiology of delirium is essential
Often multifactorial
Take heed of the vulnerable patient!- always think about the vulnerability X exposure interaction
The most important graph in medicine
High
Risk
Exp
osu
re
Low
Low
High
Sick
Not sick
Etiology of delirium:Risks
Age, age, age and age
Cognitive dysfunction- intellectual disabilities, visual impairment, depression, dementia
Prior neuropathology- stroke, tumor, vasculitis, trauma, history of trauma
Major medical/surgical illness- hip fracture, ICU stays,
Algahtani and Abdu. Neurosciences 17(3) 205 (2012)
Etiology of delirium:Exposures
Metabolic and systemic illness- sepsis, organ failure, electrolyte abnormalities, hypoxia, hypoglycemia, UTI
Endocrinopathies
CNS infections and lesions
Nutritional deficiencies- thiamine, niacin, B12, folate
Intoxication and withdrawal
Others…- heat stoke, electrocution, sleep deprivation, MEDICATIONS
Etiology of delirium:Medications
Anticholinergics/antihistamines
Analgesics
Steroids/sympathomimetics
Sedatives
Anticonvulsants
Antiarrythmics/antihypertensives
Antibiotics (PCN, cephalosporins, quiolones)
“I watch death”
Note the mnemonic “WHHHIMP”
Etiology of delirium:Life threatening causes
Wernicke’s encephalopathy
Hypoxia
Hypoglycemia
Hypertensive encephalopathy
Intracerebral hemorrhage
Meningitis/encephalitis
Poisoning
Pathophysiology of delirium:Several hypotheses
Neurotransmitter hypothesis- hypocholinergic state
i. supported by deliriogenic effects of anticholinergic medications and dementia
- dopamine (and norepinephrine) excessii. supported by intoxicating effects of numerous dopaminergic
agonists and the beneficial effects of antipsychotics
Neuroinflammatory hypothesis- elevated cortisol, elevated CRP, elevated procalcitonin
- alteration of the BBB and microglia activation disrupts brain function
Hypoxia hypothesis- disrupted oxygen supply or neurovascular coupling causing
neuronal dysfunction
Neurovascular coupling
Hughes, Patel and Pandharipande. Curr Opinion in Critical Care 2012
Examples of neuropathology associated with delirium
CT MRI
White matter hyperintensities Atrophy
Neuroimaging in delirium:Not generally recommended
Structural changes- atrophy
- vascular lesions and white matter hyperintesities
- white matter changes (evaluated with diffusion tensor MRI)
Perfusion/metabolic changes- Reduced blood flow (SPECT imaging)
- Reduced metabolism (PET imaging)
EEG- diffuse slowing with moderate amplitude common but nonspecific
- useful in ruling out non-convulsive status epilepticus, hepatic encephalopathy (triphasic waves) and some viral encephalopathies
Fox et al. PNAS 2005
Functional MRI:Defining large networks potentially disrupted in delirium
Clinical assessment of delirium:General principles
Review chart for fluctuating course, recent illness, baseline function
Review medications including PRNs
Review history of substance use, CNS pathology and mental illness
Gather collateral with emphasis on recent change in function
Physical exam findings in delirium
Hypotension- dehydration, sepsis, cardiac disease
Tachycardia- dehydration, sepsis, cardiac disease, hyperthyroidism, intoxication
Fever- infection, withdrawal states, NMS
Hypothermia- sepsis, myxedema, Wernicke’s encephalopathy
Fayes et al. J Pain Symptom Manage 30: 41 (2005)
Using the MMSE in delirium
Scores < 24 have been suggested to be a threshold
4 key questions of the MMSE- Year
- Date
- Backward spelling (“DLROW”)
- Figure copying
Clinical assessment of delirium:Laboratory tests
Recommended tests- Electrolytes, glucose, calcium, CBC, LFTs, UA, Utox and drug levels
when appropriate
Not necessarily recommended, but should be considered
- CXR, blood cultures, blood gasses, EEG
Use only in appropriate cases- Neuroimaging (structural with CT or MRI, functional with PET or
SPECT)
Clinical case:24 y/o with acute confusion
A 24 y/o male with history of bipolar disorder presents to the ED on a hot Seattle summer day with acute confusion, agitation, and aggressive behavior. He is hyperthermic and has various routine laboratory abnormalities including elevated WBCs and hypernatremia. Although poorly cooperative with the exam you note some rigidity, tremor, tachycardia, diaphoresis, and tachypnea.
Questions:1)What other labs would you like to know?2)What is a possible diagnosis?
Treatment, prevention and prognosis of delirium
Management:Basic principles
Search for the underlying cause!- Medications only treat symptoms, not etiology.
Minimize psychoactive medications
Provide supportive care- oxygen, hydration and nutrition
- positioning and mobilization
- avoid restraints
- maximize non-pharmacologic care
The goal is an alert and manageable patent, not a sedated and lethargic patient
Treating delirium:Non-pharmacologic approaches
Promote sleep hygiene- visible clock, provide light cycle, avoid night time awakenings
Low stimuli environment- reduce IV “beeps”, move away from the nursing station
Encourage family visits, consistent staffing
Minimize interrupting patient and unnecessary moves/tests
Inouye et al., A multicomponent intervention to prevent delirium in hospitalized older patients.
N Engl J Med, 1999. 340(9): p. 669-76.
Pharmacologic treatment of delirium:Use only if patient is dangerous or physically/mentally uncomfortable
Haloperidol is first line- not if concern for Parkinson’s, Lewy body or Parkinson’s Plus
syndrome
- start with 0.5 mg BID PO/IV with 0.5 mg q4 hours PRN
- IV may cause less EPS but it has a short duration of actions
Atypical antipsychotics (no IV forms)- Risperidone: start at 0.25-0.5 mg PO BID
- Olanzapine: start 2.5-5 mg PO BID (IM form available)
- Quetiapine: start at 12.5-25 mg BID (often preferred given low risk of EPS, can cause orthostasis)
- All can cause metabolic syndrome if used long term and acutely disrupt glucose management complicating diabetes treatment
Pharmacologic treatment of delirium:Guidelines regarding QTc prolongation
Potentially causing V-fib/Torsades des pointes- men: < 430 normal, 431 - 450 increased, > 451 high
- women: < 450 normal, 451 - 470 increased, > 471 high
- watch for an increase of > 30 msec from baseline
Contributing factors include- age, female gender, hx of heart disease, CHF, hepatic disease
- low K/Mg, bradycardia, alcohol use, drug use (stimulants), rapid infusion of drugs
Antipsychotics to be leery of:- Typical : pimozide, thioridazine, IV haloperidol
- Atypical : ziprasidone > quetiapine > risperidone (newer agents also)
Clinical case:24 y/o with odd behavior
A 24 y/o male with a history of schizophrenia presents with fluctuating behavior and cognitive disorganization that is different from his baseline. He is intermittently mute, postures while standing, resists movements (negativism), and engages in echolalia and echopraxia. At times he is conversant, at others fully unresponsive.
Questions:1) Is this delirium or catatonia?2) What medications might be helpful?
Clinical case:Catatonic symptoms in delirium
Catatonia has 3 or more of the following- stupor, catalepsy, waxy flexibility, mutism, negativism, posturing,
mannerisms, stereotypy, agitation, grimacing, echolalia, echopraxia
Catatonia can occur in any mental or medical disorder but should NOT be attributed exclusively to delirium
Catatonia is frequently treated with benzodiazepines which can worsen delirium
Recommendation: resolve delirium first, then deal with catatonia if it remains
Prognosis:General considerations
Will continue until the underlying cause resolves
Typically resolves in days, but can take substantially longer in those with known CNS disease
Subsyndromal symptoms can return, even after days, and caretakers should be informed
Clinical case:24 y/o with agitation and psychosis
A 24 y/o women with a history of depression is brought to the ED because of increasing disorganization and hostility. She is intermittently communicative, and when speaking is pressured and preoccupied with being chosen by god to save the world. At other times he stares off into space, mute while performing odd gestures with her hands. At other times she is tearful, angry and accuses her family of trying to poison her.
Questions:1) What is odd about this presentation?2) Why is the history of depression important here?3) What is a possible diagnosis?
Jacobowski et al. Journal of Psychiatric Practice. 19(1):15 (2013)
Clinical case:Delirious mania (Bell’s Mania)
Delirium may be present in 10-20% of manic patients
Acute onset of both manic and delirium symptoms
- psychosis and catatonic symptoms are also common
Difficult to treat with antipsychotics and mood stabilizers
ECT and benzodiazepines seem most effective
As always….rule out all medical causes of delirium
Essential take home points
Delirium is common and represents the brain under stress
Establish the patients baseline function
Always review medication and substance use
Search for an etiology and rectify
Use antipsychotics only when necessary, behavioral measures should be used first